α-synuclein overexpression in the retina leads to vision impairment and degeneration of dopaminergic amacrine cells

• Published in: Scientific reports Vol. 10; no. 1; p. 9619
• Main Authors: Marrocco, Elena, Indrieri, Alessia, Esposito, Federica, Tarallo, Valeria, Carboncino, Anna, Alvino, Filomena Grazia, De Falco, Sandro, Franco, Brunella, De Risi, Maria, De Leonibus, Elvira
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 15.06.2020; Nature Publishing Group UK
• Subjects: Acuity; alpha-Synuclein - metabolism; Amacrine cells; Amacrine Cells - metabolism; Amacrine Cells - pathology; Animals; Dihydroxyphenylalanine; Dopamine receptors; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Electroretinograms; Female; Fluorescent Antibody Technique; Levodopa; Levodopa - pharmacology; Light effects; Male; Mice; Mice, Inbred C57BL; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Parkinson's disease; Retina; Retina - drug effects; Retina - metabolism; Retina - pathology; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal ganglion cells; Synuclein; Vision; Vision Disorders - metabolism; Vision Disorders - pathology; Visual Acuity; Visual impairment
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-66497-6

The presence of α-synuclein aggregates in the retina of Parkinson's disease patients has been associated with vision impairment. In this study we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic amacrine cells (DACs) in the retina. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Before and after systemic injections of levodopa (L-DOPA), retinal responses and visual acuity-driven behavior were measured by electroretinography (ERG) and a water maze task, respectively. Amacrine cells and ganglion cells were counted at different time points after the injection. α-synuclein overexpression led to an early loss of DACs associated with a decrease of light-adapted ERG responses and visual acuity that could be rescued by systemic injections of L-DOPA. The data show that α-synuclein overexpression affects dopamine neurons in the retina. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments.